Cellular interactions and Ion channel signatures in atrial fibrillation remodeling: insights from single-cell analysis and machine learning

This study underscores the critical roles of cell distribution, cell developmental trajectories, and intercellular interactions in the structural remodeling of AF, as well as the key ion channel biomarkers involved in AF-related electrical remodeling. In terms of structural remodeling, the proportions of EF, APF, and LBCs are elevated in AF, with EF cells potentially differentiating into APF or SMC. Moreover, active EF cell signaling and the loss of EC signals in AF may be crucial for the onset and maintenance of this arrhythmia. Regarding electrical remodeling, <i>ANO1</i> and <i>GRIK2</i> have been identified as potential biomarker genes for AF. Notably, phenytoin sodium may exert therapeutic effects against AF by targeting EF subtypes. In addition, ionomycin, citalopram, and topiramate exhibit modulatory effects on ion channels, providing new potential treatment avenues. Such drug repurposing represents a rapid and efficient strategy for the discovery of novel AF therapies.